KF-1607, a Novel Pan Src Kinase Inhibitor, Attenuates Obstruction-Induced Tubulointerstitial Fibrosis in Mice

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson’s trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

Background/Aims@#Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear. @*Materials and Methods@#This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine. @*Results@#Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (P<0.005), 2.5 and 1.8 (P<0.005), and 9.3 and 5.0 (P<0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (P<0.001), 2.0 (P=0.001), and 1.3 (P=0.3), respectively. @*Conclusions@#Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.

Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. MATERIALS AND METHODS: In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. RESULTS: In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. CONCLUSION: These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

The Impact of Inosine Triphosphatase Variants on Hemoglobin Level and Sustained Virologic Response of Chronic Hepatitis C in Korean

Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.

Recurrent Auricular Keloids during Pregnancy

No abstract available.

A Case of Septic Shock by Prevotella Species associated with Acute Periapical Abscess / 감염과화학요법

A healthy 34-year-old man was admitted to the intensive care unit through the emergency room with a drowsy mentality and severe chilling. Following a diagnosis of septic shock of unknown origin, the patient was treated with broad spectrum antibiotics and massive hydration. After recovery of consciousness, he complained of a severe toothache that originated from the right lower teeth. Under dental consultation, he was diagnosed as having an acute periapical abscess of the right mandibular first molar. The patient underwent extraction and cyst enucleation. Gram negative bacilli isolated from blood culture on day 5 after admission were identified as Prevotella species. After receiving antibiotic treatment and undergoing dental procedures, the patient made a full recovery. We report on a case of septic shock due to infection by Prevotella species in association with an acute periapical abscess.

Supernumerary Nostril: A Case Report

PURPOSE: Supernumerary nostril, also known as triple nostril or accessory nostril, is one of the extremely rare congenital nasal deformities which includes an additional nostril. Since Lindsey reported the first case of a supernumerary nostril, only 34 cases of supernumerary nostril have been reported world widely. And there was no any domestic case. In the present case, we described a case of supernumerary nostril and reviewed all the literature cases of supernumerary nostril. METHODS: A 10-month-old female patient visited to the authors with an additional nostril located above her right nostril, which had been present since birth. Antenatal history was uneventful and the infant's birth was normal. On physical examination there were no other abnormalities and additional nostril was communicating with ipsilateral normal nasal cavity. We performed fistulectomy and local flap for the correction. RESULTS: After 7 months postoperatively, the patient was doing well. The functional outcome was excellent and the cosmetic result was satisfactory. During the long term follow-up for 8 years, there were no specific problems. CONCLUSION: In supernumerary nostril, preoperative evaluation of other abnormalities is very important and we advocate that corrective surgery can be performed at an early age for patient's psychosocial development.

Supernumerary Nostril: A Case Report

PURPOSE: Supernumerary nostril, also known as triple nostril or accessory nostril, is one of the extremely rare congenital nasal deformities which includes an additional nostril. Since Lindsey reported the first case of a supernumerary nostril, only 34 cases of supernumerary nostril have been reported world widely. And there was no any domestic case. In the present case, we described a case of supernumerary nostril and reviewed all the literature cases of supernumerary nostril. METHODS: A 10-month-old female patient visited to the authors with an additional nostril located above her right nostril, which had been present since birth. Antenatal history was uneventful and the infant's birth was normal. On physical examination there were no other abnormalities and additional nostril was communicating with ipsilateral normal nasal cavity. We performed fistulectomy and local flap for the correction. RESULTS: After 7 months postoperatively, the patient was doing well. The functional outcome was excellent and the cosmetic result was satisfactory. During the long term follow-up for 8 years, there were no specific problems. CONCLUSION: In supernumerary nostril, preoperative evaluation of other abnormalities is very important and we advocate that corrective surgery can be performed at an early age for patient's psychosocial development.

Herpes Simplex Virus Infection after Corrective Rhinoplasty through External Approach: Two Case Reports

PURPOSE: Eczema herpeticum, caused by herpes simplex virus, is an infectious disease involving skin and internal organs. Varieties of physiologic, psychosocial, or environmental stress reactivate reservoir virus which exists in the trigeminal nerve ganglia. Authors report rare cases of nasal eczema herpeticum following corrective rhinoplasty. METHODS: First case, 22-year-old female underwent corrective rhioplasty through an external approach in a local clinic. She developed progressive and painful erythema, nodules and vesicles on nose on the 9th day postoperatively. This unfamiliar lesion lead to a misdiagnosis as a bacterial infection, and had accelerated its progress to the trigeminal innervation of the nasal unit. Second case, a 23-year-old female underwent corrective rhinoplasty by external lateral osteotomy. Ten days after the surgery, disruption occurred on the external osteotomy site, and the ulceration gradually worsened. The surgeon misdiagnosed it as secondary bacterial infection and only an antibacterial agent was applied. RESULTS: Both cases were healed effectively without any complication with proper wound dressing and antiviral therapy, and show no sequelae during an 8-month follow-up period. CONCLUSION: Eczema herpeticum is rare in the field of plastic surgery, but it should be kept in mind that secondary bacterial infections may lead to serious complications such as full-thickness skin loss. Thus, acknowledgement of the patient's past history regarding perioral or intraoral lesion may provide the surgeon with the possible expectancy of eczema herpeticum. Thus, if anyone develops eczema herpeticum, following facial plastic surgery, early diagnosis and immediate proper antiviral therapy will allow fast recovery without serious complications.

Herpes Simplex Virus Infection after Corrective Rhinoplasty through External Approach: Two Case Reports

PURPOSE: Eczema herpeticum, caused by herpes simplex virus, is an infectious disease involving skin and internal organs. Varieties of physiologic, psychosocial, or environmental stress reactivate reservoir virus which exists in the trigeminal nerve ganglia. Authors report rare cases of nasal eczema herpeticum following corrective rhinoplasty. METHODS: First case, 22-year-old female underwent corrective rhioplasty through an external approach in a local clinic. She developed progressive and painful erythema, nodules and vesicles on nose on the 9th day postoperatively. This unfamiliar lesion lead to a misdiagnosis as a bacterial infection, and had accelerated its progress to the trigeminal innervation of the nasal unit. Second case, a 23-year-old female underwent corrective rhinoplasty by external lateral osteotomy. Ten days after the surgery, disruption occurred on the external osteotomy site, and the ulceration gradually worsened. The surgeon misdiagnosed it as secondary bacterial infection and only an antibacterial agent was applied. RESULTS: Both cases were healed effectively without any complication with proper wound dressing and antiviral therapy, and show no sequelae during an 8-month follow-up period. CONCLUSION: Eczema herpeticum is rare in the field of plastic surgery, but it should be kept in mind that secondary bacterial infections may lead to serious complications such as full-thickness skin loss. Thus, acknowledgement of the patient's past history regarding perioral or intraoral lesion may provide the surgeon with the possible expectancy of eczema herpeticum. Thus, if anyone develops eczema herpeticum, following facial plastic surgery, early diagnosis and immediate proper antiviral therapy will allow fast recovery without serious complications.

Modified Seven-flap Web Plasty for Incomplete Syndactyly

PURPOSE: Incomplete syndactyly, due to either congenital or acquired, is uncommon. Many different surgical methods have been descirbed. We introduce the modification of seven flap-plasty for incomplete syndactyly and report functional improvement after correction by modified seven flap-plasty without skin graft. MATERIALS AND METHODS: Twelve patients with an incomplete syndactyly who underwent modified seven flap-plasty were analyzed. Age ranged from one to 40-year-old (average age 21). There were 8 males and 4 females, and the degree of syndactyly was near proximal interphalangeal joint. Two different operative methods were performed. Modification I modified two half-Z flaps in parallelogram shape, and modification II modified V flap of V-M flap in Y-V flap. Functional improvements was measured by maximal abduction distance and maximal abduction angle change. RESULTS: All cases were corrected by using the modified seven flap plasty. Flap tip necrosis was found in two cases of severe burn scar patients, but did not require additional surgery. There was no specific complications. Maximal abduction distance was increased in 6 mm, and maximal abduction angle was increased in 5.8degrees. CONCLUSION: Incomplete syndactyly near proximal interphalangeal joint was corrected by modified seven flap plasty and was able to get a satisfactory result.

Toe Tissue Transfer for Reconstruction of Damaged Digits due to Electrical Burns

BACKGROUND: Electrical burns are one of the most devastating types of injuries, and can be characterized by the conduction of electric current through the deeper soft tissue such as vessels, nerves, muscles, and bones. For that reason, the extent of an electric burn is very frequently underestimated on initial impression. METHODS: From July 1999 to June 2006, we performed 15 cases of toe tissue transfer for the reconstruction of finger defects caused by electrical burns. We performed preoperative range of motion exercise, early excision, and coverage of the digital defect with toe tissue transfer. RESULTS: We obtained satisfactory results in both functional and aesthetic aspects in all 15 cases without specific complications. Static two-point discrimination results in the transferred toe cases ranged from 8 to 11 mm, with an average of 9.5 mm. The mean range of motion of the transferred toe was 20degrees to 36degrees in the distal interphalangeal joint, 16degrees to 45degrees in the proximal interphalangeal joint, and 15degrees to 35degrees in the metacarpophalangeal joint. All of the patients were relatively satisfied with the function and appearance of their new digits. CONCLUSIONS: The strategic management of electrical injury to the hands can be both challenging and complex. Because the optimal surgical method is free tissue transfer, maintenance of vascular integrity among various physiological changes works as a determining factor for the postoperative outcome following the reconstruction.

Adrenal Metastasis from Hepatocellular Carcinoma without Intrahepatic Recurrence after Hepatic Resection / 대한소화기학회지

Although the adrenal gland is a common site of metastasis from hepatocellular carcinoma (HCC), adrenal metastases are rarely seen in clinical practice because of its lower metastatic potential compared to the other malignancies. Adrenal metastases usually were detected at the time of diagnosis of primary HCC or simultaneously with intrahepatic recurrence after curative management of HCC. It is very rare that only metastatic HCC is detected without evidence of intrahepatic recurrence. Hereby, we report two cases of adrenal metastasis from HCC without intrahepatic recurrence after hepatic resection.

Interactions of Dopamine D1 and N-methyl-D-Aspartate Receptors are Required for Acute Cocaine-Evoked Nitric Oxide Efflux in the Dorsal Striatum

Alterations in nitric oxide (NO) release in response to psychostimulants in the striatum cause a plastic change contributing to the development and expression of addiction. In this study, regulation of NO efflux evoked by acute cocaine in the dorsal striatum was investigated using real-time detection of NO in vivo. We found that acute systemic injection of cocaine (20 mg/kg) increased NO efflux, which was reduced by the intrastriatal infusion of the dopamine D1 receptor antagonist, SCH23390 (7.5 nmol), and the dopamine D2 receptor agonist, quinpirole (5 nmol). Increased levels of NO efflux by acute cocaine were also reduced by the intrastriatal infusion of the N-methyl-D-aspartate (NMDA) receptor antagonists, MK801 (2 nmol) and AP5 (2 nmol). These findings suggest that interactions of dopamine D1 receptors and NMDA receptors after acute exposure to cocaine participate in the upregulation of NO efflux in the dorsal striatum.

Clinical Analysis of the Nasal Bone Fracture

PURPOSE: Nasal bone fracture is the most common facial fracture. Although nasal bone fractures are considered to be minor injuries, the incidence of post-traumatic nasal deformity remains high. This study is designed to support management and patient satisfaction by classifying the simple nasal bone fracture, and survey the care method and result, which is compared with other studies. METHODS: From May 2008 to April 2010, 334 patients with simple nasal bone fractures visited our hospital. The incidence, cause, types of nasal bone fracture, treatment, and complications are analyzed according to clinical examination, patient's record and radiographic images. RESULTS: The mean age of patients was 30 years old, with 74% of the patients having been male, and 26% were female. The highest incidence of this fracture was between late teens to late twenties. The causes of nasal bone fracture were the following: having slipped or fallen down(39%), violence(16%), sports accident(14%), traffic accident(11%), industrial accident(6%), and others(16%). Patient's radiographic images were analyzed by Stranc and Robertson classification, frontal impact plane I was 38%, plane II was 16%, plane III was 1%, lateral impact plane I was 21%, plane II was 21%, and plane III was 3%. On average, surgical treatment was performed 7.2 days after trauma under general anesthesia. Closed reduction of nasal bone fracture was performed in 99% of patients. In patients with septal injuries, septal management was performed in 76.7% of cases. Aesthetic surgery was done on same time in 24% of patients. There were some complications, such as residual nasal deformity(7.2%), nasal obstruction(0.9%) and hyposmia(0.3%). CONCLUSION: According to this study, nasal bone fractures occurred commonly in physically active age groups(age 15~29 years), as a result of having slipped or fallen down, at afternoon and at night time. And it could be treated successfully by closed reduction and septoplasty by 7 days after trauma.

Myositis Ossificans on the Nasal Dorsum: A Case Report

PURPOSE: Myositis ossificans is a benign condition of heterotopic bone formation that still requires more of its pathologic explanation. The lesions are localized predominantly to the high-risk sites of injury, involving flexor muscles of the upper limbs and thigh, but rarely in the head and neck area. METHODS: A case of a 44-year-old male patient presented with a palpable hard mass on nasal dorsum. The patient experienced a similar lesion on upper limb few years ago. On computed tomographic image, the lesion presented focal definite increase in opacity compatible to adjacent bone densitiy on nasal dorsum. RESULTS: The lesion was excised under open rhinoplasty incision. The pathologic report revealed focal bone formation and calcification within skeletal muscle. CONCLUSION: We describe a unique and only case of a myositis ossificans on nasal dorsum which is indifferent from previous concept.

Considering Spherical Aberration in Choosing the Wavefront Map for Laser Vision Correction

PURPOSE: To report the dynamic nature of human optical aberrations in the scotopic condition. METHODS: A total of 20 eyes who were candidates for laser vision correction were included in the present study. Repeated wavefront data were obtained using WavescanTM (AMO/VISX). From the wavefront analysis data, the sphere, astigmatism, average pupil size, spherical aberration, coma and trefoil were selected and used to investigate any correlation among the parameters. RESULTS: The sphere, spherical aberration, coma and pupil size showed a dynamic change in the scotopic condition. The spherical aberration and pupil size decreased by the amount of 0.10 +/- 0.04 microm and 0.55 +/- 0.37 mm as the sphere changed 1 D in myopic direction. There was significant positive correlation between the sphere and spherical aberration in 13 eyes of 9 patients (65%), between the sphere and pupil size in 5 eyes of 4 patients (25%), and between the sphere and coma in 3 eyes of 3 patients (15%). The spherical aberration decreased significantly in 4 eyes of 4 patients (20%) as the pupil size decreased. CONCLUSIONS: The optical aberration of human eyes showed a dynamic nature in the scotopic condition. In particular, there was significant correlation between the sphere and spherical aberration. The observed correlations have the potential to be used as helpful indicators to select the optimal wavefront data for the laser vision correction.

Phenotype-Genotype Association Study: From GWAS to NGS

No abstract available.

Clinical Analysis of Pediatric Facial Laceration

PURPOSE: Pediatric facial laceration takes a huge part of patients visiting emergency room and generates social attention for its proper emergency care. So much more attention should be paid to the proper treatment at emergency care unit, and furthermore, thorough survey of background information of the pediatric facial laceration may offer more proper prevention. METHODS: According to annual reports of 2009 and 2010, out of 5149 facial laceration patients who were given primary medical care at our clinic, 1452 patients were aged under 15 years old. Retrospective analysis of each pediatric facial lacerations were evaluated according to gender, age, periodic table, cause of injury, place of injury, sites of injury and so on. RESULTS: Pediatric facial laceration was found to occur mostly at 1 year old as they learn to walk and explore their environment. Evaluated analysis revealed that pediatric facial accidents occurred mostly on forehead region (75%), on Sundays, from 5 p.m. to 8 p.m., at home(61.5%). Most common cause of injury was collision(54.5%). CONCLUSION: In large group of pediatric facial laceration cases provided us with an surprising fact that accidents most commonly occur under parental supervision. This fact gives an actual understanding regarding pediatric facial laceration and more realistic approach in its prevention strategy.

Augmentation Genioplasty Using the Multiporous High Density Polyethylene(Medpor(R))

Microgenia is that the mental protuberance is small state because of symphysis did not developed properly while occlusion and size of mandible are normal. One or two-step sliding advancement genioplasty is mainly performed to make good aesthetic harmony with face, but in slight or moderate degree of microgenia patients who do not want general anesthesia or osteotomy, the multiporous high-density polyethylene(Medpor(R)) can be used. It is easy to carve and bend, and has a variety of size and shape to fit the contour of the chin anatomy. Under the local anesthesia. a vertical incision which can preserve mentalis muscle is made about 2 cm at inferior labial sulcus along inferior frenulum in the jaw midline. Subperiosteal dissection is performed to make a pocket. Seperated Medpor(R)s are inserted in each side and reassembled into one in the midline. To minimize bone erosion, implant has to be placed on the inferior side of mandible edge and fixed with screw. Bandage compression was applied for 3 days and antibiotics was treated for 7 days postoperatively. This technique has a small incision, easy procedure and faster recovery. During the follow-up period, there were no specific complications and patients were all satisfied to their result.